Seeking for the endogenous ligands for PPARγ

Peroxisome proliferators-activated receptors gamma (PPARγ) is an isoform of PPARs which are members of the nuclear receptor superfamily and are considered as key sensors of lipid and glucose homeostasis. This ligand-activated transcription factor has been intensively studied for more than a decade and the bona fide endogenous ligand remains unknown. 15-Deoxy-Δ^12,14-prostaglandin J₂ (15d-PGJ ₂) is of great interest because it affects gene transcription by binding and activating PPARγ and by covalent addition to transcription factors and signaling molecules. However, the actual concentration of 15d-PGJ₂ is several orders of magnitude below the levels required to induce many of the biological reaction attributed to this molecule. This short review will focus on 15d-PGJ₂ as a ligand of PPARγ and on other candidates of the endogenous ligand for the receptor.